Department of Animal & Avian Sciences and Department of Cell Biology & Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Cell. 2011 May 27;145(5):720-31. doi: 10.1016/j.cell.2011.04.025.
Extracellular free heme can intercalate into membranes and promote damage to cellular macromolecules. Thus it is likely that specific intercellular pathways exist for the directed transport, trafficking, and delivery of heme to cellular destinations, although none have been found to date. Here we show that Caenorhabditis elegans HRG-3 is required for the delivery of maternal heme to developing embryos. HRG-3 binds heme and is exclusively secreted by maternal intestinal cells into the interstitial fluid for transport of heme to extraintestinal cells, including oocytes. HRG-3 deficiency results either in death during embryogenesis or in developmental arrest immediately post-hatching-phenotypes that are fully suppressed by maternal but not zygotic hrg-3 expression. Our results establish a role for HRG-3 as an intercellular heme-trafficking protein.
细胞外游离血红素可以插入到膜中，并促进细胞大分子的损伤。因此，很可能存在特定的细胞间途径，用于血红素定向运输、转运和递送到细胞靶标，尽管迄今为止尚未发现任何途径。在这里，我们表明秀丽隐杆线虫 HRG-3 是将母体血红素递送到发育中的胚胎所必需的。HRG-3 结合血红素，并且仅由母体肠细胞分泌到细胞间隙中，以便将血红素转运到肠外细胞，包括卵母细胞。HRG-3 缺陷要么导致胚胎发生过程中死亡，要么导致孵化后立即发育停滞——这些表型完全被母体而非合子 hrg-3 表达所抑制。我们的结果确立了 HRG-3 作为细胞间血红素转运蛋白的作用。
